Accéder au contenu
Merck

Neuronal-enriched small extracellular vesicles trigger a PD-L1-mediated broad suppression of T cells in Parkinson's disease.

iScience (2024-07-15)
Zhichun Chen, Wenming Li, Bo Meng, Chongchong Xu, Yiqi Huang, Guanglu Li, Zhexing Wen, Jun Liu, Zixu Mao
RÉSUMÉ

Many clinical studies indicate a significant decrease of peripheral T cells in Parkinson's disease (PD). There is currently no mechanistic explanation for this important observation. Here, we found that small extracellular vesicles (sEVs) derived from in vitro and in vivo PD models suppressed IL-4 and INF-γ production from both purified CD4+ and CD8+ T cells and inhibited their activation and proliferation. Furthermore, neuronal-enriched sEVs (NEEVs) isolated from plasma of A53T-syn mice and culture media of human dopaminergic neurons carrying A53T-syn mutation also suppressed Th1 and Th2 differentiation of naive CD4+ T cells. Mechanistically, the suppressed phenotype induced by NEEVs was associated with altered programmed death ligand 1 (PD-L1) level in T cells. Blocking PD-L1 with an anti-PD-L1 antibody or a small molecule inhibitor BMS-1166 reversed T cell suppression. Our study provides the basis for exploring peripheral T cells in PD pathogenesis and as biomarkers or therapeutic targets for the disease.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
Anticorps anti-tyrosine hydroxylase, Chemicon®, from rabbit
Référence
Conditionnement
Disponibilité
Prix
Quantité
Sigma-Aldrich
Protease Inhibitor Cocktail powder, for general use, lyophilized powder
Référence
Conditionnement
Disponibilité
Prix
Quantité
Sigma-Aldrich
Anticorps anti-Ptx3/PITX3, Chemicon®, from rabbit
Référence
Conditionnement
Disponibilité
Prix
Quantité